. Author manuscript; available in PMC: 2017 Oct 28.

Published in final edited form as: J Control Release. 2016 Jan 14;240:349–363. doi: 10.1016/j.jconrel.2016.01.026

Table 1.

Controlled release studies that affect the M1-M2 balance in vascularization and bone regeneration.

Materials	Controlled release methods	Cytokine/Drug	Role and in vivo Effect	Reference
Decellularized bone scaffold	Biotin-avidin binding	IFNγ	Promotes M1 macrophages Increases blood vessels in vivo	[30]
Decellularized bone scaffold	Biotin-avidin binding	IL-4	Promotes M2 macrophages	[30]
Collagen scaffold	Adsorption	Lipopolysaccharide (LPS)	Promotes M1 macrophages No vascularization in vivo but high inflammatory cell infiltration into scaffolds	[63]
poly(L-lactic acid) oligomer grafted gelatin hydrogels	Dissolved in poly(L-lactic acid) oligomer grafted gelatin	SEW2871 (Sphingosine-1 phosphate (S1P) receptor agonist)	Promotes macrophage migration When combined with platelet-rich plasma (PRP), increases bone regeneration in vivo compared to either agent alone	[67]
Nanofibers of poly(DL-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL)	Dissolved in PCL/PLGA	FTY720 (S1P receptor agonist)	Promotes M2 macrophages Increases vascularization and bone regeneration in vivo	[66]
PLGA thin film	Simple loading in film	FTY720 (S1P receptor agonist)	Promotes M2 macrophages Increases arteriolar diameter and capillary tortuosity in vivo	[65]